anemia types and how to manage each type
- 8. Fe absorption Favoured by Reduced by Dietary factors: Dietary factors: - Haem iron (meat, fish). - Decreased haem iron. - animal foods. - Decreased animal foods. - Ferrous iron salts. - Ferric iron salts. Luminal factors: Luminal factors: - Acid pH. - Alkalis (pancreatic secretion). - Low molecular weight soluble chelates (vitamin C, sugars, amino acids). - Insoluble iron complexes (phytates, tannates in tea). Systemic factors: Systemic factors: - Iron deficiency. - Decreased erythropoiesis. - Erythropoiesis (after haemorrhage). - Inflammatory disorders. - Ineffective erythropoiesis. - Pregnancy. - Hypoxia
- 11. Diagnostic methods for investigating iron metabolism 1- Serum ferritin 2-Serum iron and iron binding capacity 3-BM aspiration: Staining of the bone marrow for iron gives an indication of RE iron stores as well as erythroblast iron. 4- Soluble transferrin receptor level (sTFR)
- 12. Iron deficiency anaemia Definition Iron deficiency denotes a deficit in total body iron resulting from a sustained increase in iron requirements over iron supply .
- 13. Tissue effects of iron deficiency • When iron deficiency is severe and chronic, widespread tissue changes may be present including koilonychia, angular stomatitis, glossitis, pharyngeal web (plummer vinson syndrome)
- 14. • In severe iron deficiency anaemia, there is a fall in the level of iron dependent enzymes with poor lymphocyte transformation and diminished cell mediated immunity and impaired intracellular killing of bacteria by neutrophils. • Infants with iron deficiency anaemia may have impaired mental development and function, and this deficit may not be completely restored by iron therapy.
- 15. Diagnosis 1- CBC • Hypochromic microcytic anaemia. • Mild ovalocytosis, target cells, anisopoikilocytosis
- 16. 2- BM • Absent sideroblasts. • or absent hemosiderin by Prussian blue staining. 3-Serum : • serum iron, TIBC, percentage saturation < 15%. • serum ferritin. , level. of sTFR
- 17. • Special studies 1- If GI loss is suspected, multiple stools should be tested for occult blood. Tests are insensitive to < 5-10 ml blood loss per day. 2- Radiographic / endoscopic studies may detect the source of gastrointestinal bleeding.
- 18. Treatment • 1- Oral iron therapy Dietary sources are insufficient for treatment. Non enteric-coated forms should be used. Daily total of 150-200 mg elemental iron in 3 to 4 doses, each 1 hour before meals. (200 mg of ferrous sulphate contains 60 mg of iron and 300 mg of ferrous gluconate contains 36 mg of iron). A few patients will have gastrointestinal intolerance to pills with constipation, diarrhea and or metallic taste and require total daily dose reduction or change of oral iron preparation.
- 19. • 2- Parentral iron therapy Indications Malabsorption. Intolerance to oral iron (colitis,enteritis). Need of response in a short time Patient uncooperative or unavailable for follow up.
- 20. Aplastic anaemia and bone marrow failure
- 21. Aplastic anaemia is a severe , life-threatening syndrome in which production of erythrocytes, platelets, and leukocytes is diminished or absent This failure reflects a quantitative and / or qualitative defect in the stem cells.
- 22. The aetiologic classification of aplastic anaemia include: A- Primary (Idiopathic) B- Secondary to chemical and physical agents : * Irradiations * Chemicals as benzene, insecticides, hair dyes * Drugs as chloramphenicol, sulfa drugs, antihistaminics, antithyroid drugs, gold, chemotherapeutic agents, some antibiotics, and carbonic anhydrase inhibitors.
- 23. C- Infections in particular : EBV, CMV and viral hepatitis particularly non A, non B. D- Paroxysmal nocturnal haemoglobinuria. E- Hereditary as Fanconi's anaemia. F- Pure red cell aplasia : * Congenital (Diamond-Blackfan syndrome) * Acquired e.g. with thymoma.
- 24. Clinical picture : The onset of symptoms in aplastic anaemia is usually insidious and related to the cytopenias. The most common initial sign is bleeding. Anaemia and infection may occur separately, or in combination with the bleeding. Hepatosplenomegaly and lymphadenopathy are absent.
- 25. Laboratory examination : Characteristically, the haemoglobin, white blood count and platelet count are decreased to a varying extent in aplastic anaemia. Examination of the peripheral blood will reveal normochromic normocytic anemia and decreased numbers of platelets and granulocytes. .
- 26. Bone marrow aspiration in " classic " aplastic anaemia often results in a dry tap. Bone marrow biopsy is essential and most commonly reveals a marked hypocellular marrow with a reduction in all myeloid, erythroid and megakaryocytic elements. . Some patients show a scattered foci of normocellular or hypercellular marrow (hot spots).
- 27. Prognosis and therapy : The prognosis of untreated aplastic anaemia is poor. Only 10% may show spontaneous complete recovery. About 70% of the patients die within 5 years of diagnosis if not treated. The principles of treatment include : (1) Removal of the causative agent. (2) Management of infections. Infection is the commonest cause of death in aplastic anaemia. Aggressive antibiotic therapy
- 28. (3) Blood product support : i- red cell transfusions. ii- platelet support. (4) Immunsuppressive therapy The use of these agents is based on the fact that an immune reaction is the cause of idiopathic aplastic anaemia • Cyclosporin • ATG (antithymocyte globulin, rabbit or horse)
- 29. (5) Therapy to stimulate the marrow : eltrombopag (6) Stem cell transplantation In severe cases or failure of other lines Matched HLA sibling is required and young fit patient
- 30. Megaloblastic anaemia: Folic acid and vitamin B12 deficiency
- 31. • Folic acid and cobalamin are B-group vitamins that play an essential role in many cellular processes. • Deficiency in one or both of these vitamins causes megaloblastic anaemia. • Megaloblasts occur when inhibition of DNA synthesis causes asynchronous maturation between the nucleus and the cytoplasm.
- 34. Cobalamin is absorbed in the digestive system in three stages: Stomach: Cobalamin in food is bound to proteins from which it is released by the action of gastric acid and pepsin and rapidly taken up by TC l (haptocorrin), which carries it to the duodenum.
- 35. • Duodenum and jejunum: The alkalizing action of the pancreatic juices together with the action of the pancreatic enzymes (tripsin, chymotrypsin and elastase) degrade the TC I and release the cobalamin, which is now taken up by the intrinsic factor (IF). IF is produced by the parietal cells of the fundus and cardia of the stomach. It protect the cobalamin and carries it to the ileum. Ileum: The IF-cobalamin complex binds to cubilin and is taken up into the enterocyte by means of a calcium-dependent passive transport mechanism.
- 36. Pathophysiology of megaloblastic anemia • pathophysiology of this group of anaemias has its origins in asynchronous maturation between the nucleus and the cytoplasm leading to intramedullary apoptosis of hematopoietic precursor cells.
- 37. Causes of B12 deficiency • CAUSES VEGANS STOMACH disease (pernicious anemia, gastrectomy, congenital def of IF) Small intestinal disease ( celiac, crohn’s, tropical spru, resection) Transcobalamine II deficiency Excess NO which inhibits vitamin B12
- 38. Causes of folate deficiency • Nutritional • Increased demand (growth, pregnancy, chronic hemolytic anemia) • Malabsorption syndromes
- 39. Presentation • Glossitis and oral ulcers • Mild elevation of bilirubin (jaundice) • Neurological symptoms (only in B12 deficiency) subacute combined generation of the spinal cord i.e spastic paraparesis and positive Romberg’s sign (loss of deep sensations) Due to accumulation of methylmalonyl-CoA which impair synthesis of myelin
- 40. • Peripheral blood samples. The most notable findings are macrocytosis and hypersegmented neutrophils. • Biochemistry tests. These show ineffective haematopoiesis, characterized by intramedullary haemolysis, such as: elevated indirect bilirubin and lactate dehydrogenase (LDH). • Low serum B 12 and /or cellular folate • High MMA in B 12 deficiency
- 41. • Bone marrow aspiration: Megaloblastic changes occur in the morphology of the erythrocytic and myelocytic series. Red cell precursors are enlarged and nucleus/cytoplasm maturation is asynchronous. This latter is characterized by immature nuclei (larger, with open or lax chromatin) and mature cytoplasm (with its normal red hemoglobulinised colour). Megaloblasts in the myelocytic series manifest as larger precursors.A less common finding is the presence of hyperdiploid megakaryocytes. • Investigations for the cause; upper GI endoscopy , CT enterocolonography
- 42. • B12 supplementation Either IM or sublingual for 2 weeks • Folate 5 mg /day for 4 months • Higher doses are needed in cases with malabsorption • Folate should not be started before B12 because this will exaggerate the neurological symptoms
- 44. TYPES Inherited Defect in Hb ..thalassemia, sickle cell disease Defect in RBC membrane Herediiatry spherocytosis Defect in RBC enzymes G6PD deficiency, pyruvate kinase deficiency
- 45. Acquired • Immune • Non-immune PNH paroxysmal nocturnal hemoglobinuria MAHA microangiopathic hemolytic anemia mechanical march H, prosthetic valve Infection mycoplasma, malaria Drug-induced
- 46. HEREDITARY SPHEROCYTOSIS Hereditary spherocytosis (HS) is a congenital haemolytic disorder characterized by an inherited defect in the red cell membrane cytoskeleton leading to the formation of spherocytic red cells. Spherocytes, being less deformable than normal red cells, are trapped and destroyed in the spleen. Although most common mode of inheritance is autosomal dominant, autosomal recessive transmission occurs in some cases.
- 48. Normally, lipid bilayer of the red cell membrane is anchored to the underlying skeleton by two major linkages. The first linkage involves interaction of ankyrin with spectrin in skeleton and band 3 in the bilayer. The second attachment between skeleton and bilayer provided by glycophorin C and protein 4.1. Deficiency in any of these interactions causes weakening of contact between lipid bilayer and skeleton. This causes decrease in surface area of red cell relative to volume with resultant spherocyte formation. HS may result from deficiency of following proteins-spectrin, ankyrin, band 3, and protein 4.2.
- 49. Molecular basis of hereditary spherocytosis and elliptocytosis. Hereditary spherocytosis Ankyrin deficiency or abnormalities (most common cause – about 50% of patients) ■ α- or β-spectrin deficiency or abnormalities Band 3 abnormalities protein 4.2 abnormalities Hereditary elliptocytosis α- or β-spectrin mutants leading to defective spectrin dimer formation α- or β-spectrin mutants leading to defective spectrin– ankyrin associations Protein 4.1 deficiency or abnormality South-East Asian ovalocytosis band 3 deletion
- 50. Clinical features Majority of patients present in childhood with mild to moderate anaemia, intermittent jaundice, gall stones and enlarged spleen. In some patients, clinical feature are mild or entirely absent. Rarely hereditary spherocytosis may present as a severe haemolytic anaemia requiring regular transfusion support.
- 51. • Laboratory features In most patients, anaemia is usually mild to moderate. Reticulocytosis is present. On blood smear examination, characteristic feature is spherocytosis. Diagnostic test : Osmotic fragility test
- 52. Treatment of severe HS is splenectomy. Administration of folate is necessary in moderate or severe disease to prevent megaloblastic anaemia due to increased erythrocyte turnover.
- 53. Thalassaemia The thalassaemias are heterogeneous group of inherited disorders of haemoglobin characterized by reduced or absent production of one of the globin chains.
- 54. Classification of Thalassaemias The classification of thalassaemias is based on: (1) the type of globin chain that is deficiently synthesized (alpha ad beta), or (2) clinical expression of the disease. (TDT,NTDT)
- 55. Thalassaemias: There is a single globin locus on each chromosome (number 11) and as a humans are diploid there are two genes. thalassaemias are classified into two major types: 0 thalassaemia and + thalassaemia. 0 thalassaemia is characterized by complete absence of chain synthesis, while in + thalassaemia chain synthesis is reduced but not completely lacking. Usually individuals having one normal and one abnormal globin gene have thalassaemia minor while persons in whom both globin genes are abnormal have thalassaemia major.
- 56. thalassaemias There are two gene loci on each chromosome no.16 and since humans are diploid there are four genes. The normal genotype is written as /. . Most cases of thalassaemias result from gene deletions, while most thalassemias are caused by mutations
- 57. Presentation 1. Anaemia: In thalassaemia major the underlying genetic defect is responsible for inability of erythroid cells to synthesize adequate amounts of globin chains leading to microcytic hypochromic red cells. This causes excessive accumulation of free . The unbound chains precipitate within erythroblasts and red cells, leading to the lysis of erythroblasts and red cells in the bone marrow (ineffective erythropoiesis). The red cells containing chain aggregates have reduced flexibility and are trapped in the spleen. Haemoglobin F is the predominant haemoglobin in thalassaemia, thus exacerbates tissue hypoxia
- 58. 2. EXTRAMEDULLARY HEMATOPOIESIS Severe anaemia and tissue hypoxia stimulate erythropoietic drive and cause extreme bone marrow hyperplasia. • HEPATOSPLENOMEGALY • Skeletal changes: Expansion of hyperactive bone marrow causes weakening and deformities of skull and of facial bones (THALASSEMIC FACIES, due to raised maxilla and frontal bossing). Thinning of cortex may lead to pathological fractures. • Patient has characteristic bronze skin (anemia, jaundice and hemosiderosis)
- 59. • 3. Iron overload: Iron absorption from the intestine is increased in thalassaemia major due to ineffective erythropoiesis leading to increased hepcidin secretion, Chronic regular blood transfusion therapy as well as chronic hemolysis.
- 60. Manifestations of iron overload include: diabetes mellitus, gonadal dysfunction hepatocellular damage with cirrhosis, insulin-dependent diabetes mellitus, hypoparathyroidism, hypothyroidism and cardiac failure. 4. Chronic transfusion therapy is also associated with risk of transmission of viral infections such as human immunodeficiency virus (HIV), and hepatitis B and C viruses (HBV and HCV).
- 61. Laboratory features : Peripheral blood examination: Patients presents with severe anaemia ,. Anaemia is typically microcytic and hypochromic Haemoglogin electrophoresis: this characteristically shows low HbA1, elevated HbF (10-98%). HbA2 may be normal or increased. Other investigations:. Ferritin is increased. Unconjugated S. bilirubin and reticulocytes are increased Inv for complications Echo, MRI liver to detect iron overload Blood sugar, HbA1c Thyroid functions Parathyroid fn Pituitary fn DEXA scan to detect osteoporosis
- 62. Thalassaemia trait This is the heterozygous carrier state of thalassaemia characterized by little or no anaemia. Patients are usually asymptomatic but may develop anaemia during infections or pregnancy. Laboratory features: Haemoglobin level is either normal or mildly decreased and is generally not less than 9.0 gms/dl. Red blood cells characteristically show reduced MCV and reduced MCH. No clinical symptoms, mild increase in HbA2
- 63. Thalassaemias Human have four globin genes, two on each chromosome no. 16. There are three main clinical forms of thalassaemias; Haemoglobin Bart’s: absent chains. Incompatible with life (hydrops foetalis) syndrome, Haemoglobin H disease, and thalassaemia carrier state.
- 64. Haemoglobin H disease Hb H disease most commonly develops when both 0 and + thalassaemias are inherited (--/-) i.e. there is deletion of 3 genes. Due to marked deficiency of chain synthesis, tetramers of chains (4) are formed (HbH). They are more stable and more soluble than tetramers of chains found in thalassaemia; ineffective erythropoiesis is therefore not a significant factor in the genesis of anaemia, chain tetramers precipitate in older red cells and form red cell inclusions; these red cells are destroyed in spleen.
- 65. thalassemia carrier states: These are asymptomatic forms of thalassaemias. They are of two main forms: 0 thalassaemia trait (--/) and + thalassaemia trait (-/). 0 thalassaemia trait (--/): Since it is asymptomatic, this condition is usually detected during routine haematological studies or during family studies of a person suffering from thalassaemia.
- 66. Treatment Regular red cell transfusions and chelation therapy for iron overload are the cornerstones of therapy for thalassaemia. Blood transfusion: Regular transfusion therapy so as to maintain the haemoglobin concentration constantly above 9.5 to 10.0 grams/dl. This form of therapy radically improved the quality of life of thalassaemic patients. The aim of this therapy is to prevent anaemia and hypoxia and to suppress endogenous erythropoiesis.
- 67. • Luspatrecept anti TGFB , increase erytrhropoiesis • Iron chelation therapy is usually started at the age of 3 years. The drug employed for the treatment of iron overload is desferrioxamine (DF), an iron chelator that is given along with vitamin C to promote iron excretion. It is preferably administered by infusion pump 40-60 mg/kg body weight subcutaneously daily for 12 hours for 5-6 days a week. • adverse reactions such as convulsions, coma, cataracts, retinal damage, deafness, impairment of growth, and infections by Yersinia.
- 68. Deferiprone: major side effects are agranulocytosis, arthropathy, and possible hepatic fibrosis. Deferaxirox: given by oral administration dose 20-40 mg/kg/day. Main side effects are GIT troubles, renal impairement. Splenectomy: in hypersplenism.Due to the risk of sepsis, splenectomy should be avoided in young age. Post- splenectomy, pneumococcal, H. influenza, and meningococcal vaccines and penicillin prophylaxis are necessary.
- 69. General measures: These include folic acid supplementation, hormone replacement therapy in endocrine failure. Haematopoietic stem cell transplantation: it is the only form of therapy that can cure the disease. Gene therapy-This consists of introduction of normal gene in stem cells to replace the abnormal gene.(under research)
- 70. Sickle cell disease Sickle shaped RBCs
- 71. Genetics The sickle cell disease results from inheritance of sickle cell gene that codes for abnormal globin chain. There is change of a single base A T in the sixth codon of globin gene so that there is substitution of thymine for adenine. This in turn results in substitution of valine for glutamic acid at position 6 of polypeptide chain. The amino acid substitution in HbS is represented as 6 Glu Val. The resultant hemoglobin has sticky features upon deoxygenation, this leads to polymerization of Hb chains and formation of sickle shaped cells
- 73. Inheritance Hb SS Hb AS Homozygous heterozygous Sickle cell disease sickle cell trait
- 74. Factors which influence sickling • Intracellular concentration of HbS and of other haemoglobins: There is a direct relationship between the amount of HbS in the red cell and propensity of red cells to sickle. • Mean corpuscular haemoglobin concentration (MCHC): Increased MCHC due to cellular dehydration favours the intermolecular contact between HbS and enhances polymerization. • Decreased oxygen tension: The most important determinant affecting sickling is deoxygenation Amount of hypoxia required to induce sickling depends on the proportion of HbS.
- 75. Other factors • Temperature: Cold induces vasoconstriction and increases sickling. • Low pH: Decrease in pH (acidosis) increases sickling probably by inducing the deoxy state of haemoglobin.
- 76. • Pathology 1. Hemolysis 2. Obstruction of microcirculation 3. Injury to endothelial cells 4. Growth and development 5. Infections 6. No splenomegaly
- 78. • Growth These are considerably impaired in children with sickle cell anaemia • splenomegaly: Splenomegaly is present in infants and young children and is caused by reticuloendothelial hyperplasia. In sickle cell anaemia, in later life, spleen becomes small and fibrotic due to repeated splenic infarctions Infections: Children (esp. < 5 yrs) With sickle cell anaemia are susceptible to fulminant infections by a variety of organisms especially Streptococcus pneumonia (sepsis, meningitis), Salmonella (osteomyelitis) Esch. Coli, H.influenzae, and Shigella. Increased risk of infections in sickle cell anaemia is due to impairment of splenic phagocytic function
- 79. Clinical presentation Usually at 6 months of age after depletion of HB F 1.Pain due to avascular necrosis of bones Hands and feet (dactylitis) children Spine Long bones
- 80. Dactylitis
- 81. 2.vASOOCCLUSION • VOC; VASOOCCLUSIVE CRISIS Generalized Bony pains , patient could be bed ridden because of pain Usually in stress condition e.g, infection or dehydration • Stroke • Renal impairment (Chronic kidney disease or acute papillary necrosis) • Retinopathy • Splenic atrophy (hyposplenism) • Pulmonary hypertension, ACS; acute chest syndrome
- 82. Acute chest syndrome • Acute insult of dyspnoea, cough, fever, • lung infiltrate in chest radiograph • Я O2, ventilation if needed Transfusion, Exchange Transfusion
- 83. 3.Anemia • Aplastic crisis Due to parvovirus B19 infection • Megaloblastic crisis Due to folate deficiency • Hemolytic crisis Increased rate of red cell destruction over the chronic haemolytic state • Sequestration crisis Splenic sequestration crisis: Sudden and massive accumulation of blood in spleen causes rapid increase in size of spleen over a period of several hours, progressive anaemia, and circulatory failure.
- 84. 4.Other • Leg ulcers • Gall stones • Priapism Prolonged Painful erection due to obstruction of penile vessels
- 85. Laboratory features 1) Peripheral blood examination: Anaemia is usually moderate with haemoglobin concentration ranging between 6 and 9 gm/dl. Anaemia is normocytic and normochromic, sickled cells on the blood smear. 2) Reticulocyte count is increased. 3) Unconjugated S. bilirubin is increased. 4) Identification of HbS: haemoglobin electrophoresis.
- 86. TREATMENT • Measures to prevent vasoocculusive crises include early detection and treatment of infections and good hydration .Pneumococcal vaccine, influenza vaccine and penicillin prophylaxis are indicated during early childhood. • Treatment of vaso-occlusive episode involves relieving pain by rest and analgesics, keeping patient warm, maintaining adequate fluid intake, oxygenation, and treatment of infections.
- 87. • Acute chest syndrome: Patients with low oxygen saturation level can benefit from exchange transfusion. Patients are given adequate, O2 and broad-spectrum antibiotics. • Transfusion therapy: Packed red ell transfusion to improve oxygen-carrying capacity are required during symptomatic anaemia. • Hydroxyurea increases production of HbF and reduces number and severity of crises. As HbF does not participate with HbS in sickling process, polymerization of HbS is retarded. • Haematopoietic stem cell transplantation is the only form of therapy that can cure the disease
- 88. Metabolic RBC disorder G6PD deficiency (Favism) • G6PD deficiency is an X-linked hereditary disease Most common in MEN,,,very rare in women African and Meditteranian area • G6PD is vital in HMS responsible for reduction of glutathione which protects the cell from oxidative stress and O2 free radicles • Reduction in the enzyme results in hemolysis most commonly secondary to oxidative stress ingestion of drugs or fava beans or in the form of CHA or neonatal jaundice
- 90. • NADPH is required for continuous supply of reduced glutathione (GSH). GSH detoxifies harmful hydrogen peroxide or H2O2 to water .In G6PD deficiency, sufficient glutathione is not available to remove H2O2. • Accumulation of H2O2 causes oxidation of haemoglobin and subsequent denaturation and precipitation of globin chains. This leads to the formation of Heinz bodies. Such red cells are rigid and are trapped in the spleen (chronic hemolytic anemia)
- 91. • haemolysis usually develops after exposure to oxidant stress, such as drugs or infection. There is usually sudden development of pallor, jaundice, and dark-coloured urine (due to haemoglobinuria) 1-3 days after exposure to the drug. Hypotension and acute renal failure may develop in severe cases • Favism (precipitation of haemolysis by ingestion of fava beans) is a unique feature occurring in individuals in Mediterranean and Arab countries. Fava beans contain oxidants that cause haemolysis hours or days following ingestion; it may be fatal.
- 92. Table : Common drugs and chemicals causing haemolysis in G6PD deficiency Antimalarials: Primaquine, Chloroquine, Quinacrine, Pamaquine Antibacterials: Sulfacetamide, Sulfamethoxazole, Sulfanilamide, Sulfapyridine, Nalidixic acid, Nitrofurantion, Furazolidone, Dapsone Analgesics: Acetanilid, Aspirin, Phenacetin Others: Phenylhydrazine, Ascorbic acid, Vit K (water-soluble), Methylene blue, Naphthalene (moth balls).
- 93. Clinical manifestations of G6PD deficiency Neonatal jaundice. Drug-induced haemolytic anaemia. Haemolysis following infection. Favism. Chronic haemolytic anaemia.
- 94. • Laboratory features Evidence of haemolysis During haemolysis, general features of haemolytic anaemia are present. Peripheral blood smear shows fragmented red cells, bite cells, unconjugated hyperbilirubinaemia, haemoglobinemia, haemoglobinuria and decreased or absent haptoglobin
- 95. Tests for detection of G6PD deficiency Qualitative test for enzyme activity Fluorescent spot test Quantitative assay of G6PD • in acute conditions, after recovery of the anemia
- 96. Treatment Treatment during haemolytic attack is supportive. Blood transfusion may be indicated in severe cases. Adequate urinary output should be maintained to prevent renal damage due to haemoglobinuria. Patients should be instructed to avoid oxidant drugs that precipitate haemolysis. Prompt treatment of infections is essential.
- 97. Classification of immune haemolytic anaemias 1. Autoimmune Warm-reactive antibody type. Cold-reactive antibody type. 2. Alloimmune Haemolytic disease of newborn-Rh or ABO. 3. Drug-induced
- 98. Classification of autoimmune haemolytic anaemias 1) Warm antibody type (antibody maximally active at 37C and mostly IgG) Primary (Idiopathic) Secondary: Autoimmune disorders (e.g. systemic lupus erythematosus) Neoplastic disorders (lymphproliferative disorders like chronic lymphocytic leukaemia and malignant lymphoma, ovarian teratoma)
- 99. 2) Cold antibody type (antibody maximally active at 0 to 4C) Cold agglutinin disease (cold-reactive antibody is IgM) Primary Secondary (Infections like Mycoplasma pneumonia. EBV, CMV, malaria, Lymphoproliferative disorders). 3) Paroxysmal cold haemoglobinuria (cold-reactive antibody is IgG) primary Secondary to infections
- 100. Autoimmune haemolytic anaemias due to warm-reacting autoantibodies This is the most common form of AIHA. In this type, IgG antibodies bind to red cell membrane and are recognized by specific receptors on macrophages. IgG-coated red cells are trapped in the spleen. Macrophages may completely phagocytose the red cell or may remove a small part of the membrane; in the latter case, loss of surface area causes formation of a microspherocyte.
- 101. Some such red cells escape into the circulation and can be recognized on peripheral blood smear. Spherocytes are rigid and are sequestered and destroyed during subsequent passages through spleen.
- 102. Presentation Symptoms of anaemia, icterus, and splenomegaly. In secondary AIHA, clinical features of underlying disease predominate. Laboratory features Peripheral blood examination: This shows variable degree of anaemia, microspherocytosis of red cells, and reticulocytosis and nucleated red cells may be present. Unconjugated serum bilirubin is elevated. Platelet count is normal. In the presence of thrombocytopaenia, Evans’ syndrome should be considered.
- 103. Antiglobulin (Coombs’) test: This test determines whether haemolysis has an immunological basis. There are two types of antiglobulin test-direct and indirect. Direct antiglobulin test (DAT) is used to demonstrate antibodies attached to red cells in vivo.
- 105. Treatment Underling diseases should be found and appropriately treated. Majority of patients respond to corticosteroids (1 mg/kg body weight/day). Steroid inhibit macrophage phagocytosis and reduce synthesis of antibodies. Splenectomy is indicated when improvement does not occur with corticosteroids. Splenectomy removes the major site of red cell destruction in AIHA.
- 106. • Immunosuppressive therapy (azathioprine or cyclophosphamide) may be of benefit in cases unresponsive to steroids and splenectomy. • Blood transfusion: Blood transfusion is given only when absolutely essential. It is difficult to obtain serologically compatible blood because antibody in the patient’s serum is a’panagglutinin’ and reacts with red cells from most donors. Therefore, on cross matching all the blood units are found to be incompatible. • Rituximab anti CD20.
- 107. Autoimmune hemolytic anemias due to cold-reacting autoantibodies This is caused by those autoantibodies which react with red cells maximally in cold (0-4C) and which also retain their immunologic reactivity at higher temperatures (30C). Usually of IgM subtype and complement C3 Hemolysis occurs intravascular or in liver.
- 108. Cold agglutinin disease Cold-reactive antibodies or agglutinins are usually of IgM class. Increased production of polyclonal IgM cold agglutinins occurs in Epstein-Barr virus and mycoplasma infetions commonly. Occasionally in large cell lymphoma, monoclonal IgM cold agglutinins are increased. pain and bluish coloring of the hands and feet
- 111. Laboratory features: Anemia is commonly mild to moderate but may be severe. Unconjugated serum bilirubin is elevated. Autoagglutination of red cells is a characteristic features. It can be observed on peripheral blood smear. The DAT (coomb’s) employing anticomplement (anti-C3) reagent is positive
- 112. Treatment • Underlying cause should be identified and treated (e.g. lymphoma). • Exposure to cold should be avoided. • Corticosteroids and splenectomy are not helpful. • Cytotoxic therapy may reduce immunoglobulin production and thus decrease red cell destruction.
- 113. • Plasmapheresis to reduce circulating antibody level is a temporary measure. • Transfused red cells are destroyed by cold antibodies. Therefore, transfusions should be given only when absolutely essential with warming of the blood.
- 114. Types Warm type cold type IgG IgM or Complement Hemolysis at 37 at lower temp 0-4 Spleen intravascular Coomb’s test ++ + Positive with IgG C3 idiopathic or 2ry usually 2ry
- 115. Mechanical hemolytic anemia Physical trauma of RBCs • March hemoglobinuria • Prosthetic valve Microangiopathic hemolytic anemia (MAHA) • disseminated intravascular coagulopathy • thrombotic thrombocytopenia purpura